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2016-02-25
2024-05-08
2024-11-11
16
NCT02671890
Mayo Clinic
Mayo Clinic
INTERVENTIONAL
Disulfiram and Chemotherapy in Treating Patients With Refractory Solid Tumors or Metastatic Pancreatic Cancer
This partially randomized phase I trial studies the side effects and best dose of disulfiram when given together with chemotherapy in treating patients with a solid tumor that does not respond to treatment (refractory) or pancreatic cancer that has spread to other places in the body (metastatic) and to compare whether disulfiram and chemotherapy may reduce tumor induced muscle loss. Weight loss occurs in pancreatic cancer patients and is common in a multitude of other cancers. Patients with metastatic cancer and weight loss sometimes are not able to receive treatment due to physical weakness or debility. Disulfiram is a potential inhibitor of muscle degradation and may reduce tumor induced muscle wasting. Disulfiram may also help chemotherapy work better by making tumor cells more sensitive to the drug. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving chemotherapy with or without disulfiram is a better treatment for refractory solid tumors or metastatic pancreatic cancer.
PRIMARY OBJECTIVE: I. To determine the maximally tolerated dose (MTD) of the combination of disulfiram and gemcitabine (gemcitabine hydrochloride) in unresectable solid tumor cancer patients (Cohort 1). SECONDARY OBJECTIVES: I. To describe the adverse event profile associated with this combination of disulfiram and chemotherapy (Cohort 2). II. To describe changes in muscle area at the L3 level from baseline to 28 to 60 days from the baseline computed tomography (CT) scan in patients treated with disulfiram/chemotherapy and with placebo/chemotherapy (Cohort 2). III. To describe changes in fist-grip strength from baseline to 28 to 35 days of treatment with disulfiram/gemcitabine and with placebo/chemotherapy (Cohort 2). IV. To describe overall survival of pancreas cancer patients who disulfiram/chemotherapy or placebo/chemotherapy (Cohort 2). V. To estimate the response rate per Response Evaluation Criteria in Solid Tumors (RECIST) criteria around 1 month post-treatment in patients who receive disulfiram/chemotherapy and placebo/chemotherapy (Cohort 2). CORRELATIVE OBJECTIVE: I. To assess the effect of disulfiram and chemotherapy on the ubiquitin proteasome and autophagy pathways within muscle, as assessed by means of muscle biopsies performed at baseline and after 28 to 35 days of treatment (Cohort 2) (this is for Mayo only patients and can be waived upon permission from the principal investigator [PI]). OUTLINE: This is a phase I, dose-escalation study of disulfiram. COHORT I: Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1, 8, and 15 and disulfiram orally (PO) on days 1-28 or days 1-35. COHORT II: Patients receive chemotherapy at the discretion of the treating oncologist and disulfiram PO on days 1-28 or days 1-35. After completion of study treatment, patients are followed up at 30 days, and then every 6 months for 3 years.
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
| Study Registration Dates | Results Reporting Dates | Study Record Updates |
|---|---|---|
2016-01-29 | N/A | 2025-01-06 |
2016-01-29 | N/A | 2025-01-07 |
2016-02-02 | N/A | 2025-01 |
This section provides details of the study plan, including how the study is designed and what the study is measuring.
Primary Purpose:
Treatment
Allocation:
Non Randomized
Interventional Model:
Parallel
Masking:
None
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
|---|---|
| EXPERIMENTAL: Cohort I (gemcitabine hydrochloride and disulfiram) Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and disulfiram PO on days 1-28 or days 1-35. | DRUG: Disulfiram
DRUG: Gemcitabine Hydrochloride
OTHER: Laboratory Biomarker Analysis
|
| EXPERIMENTAL: Cohort II (chemotherapy and disulfiram) Patients receive chemotherapy at the discretion of the treating oncologist and disulfiram PO on days 1-28 or days 1-35. | DRUG: Chemotherapy DRUG: Disulfiram
OTHER: Laboratory Biomarker Analysis
|
| Primary Outcome Measures | Measure Description | Time Frame |
|---|---|---|
| Maximum tolerated dose (MTD) (Cohort I) | MTD is defined as the dose level below the lowest dose that induces dose limiting toxicity (DLT) in at least one-third of patients (at least 2 of a maximum of 6 new patients). | 28 days |
| Secondary Outcome Measures | Measure Description | Time Frame |
|---|---|---|
| Adverse events profile (Cohort I and II) | The number and severity of all adverse events (overall, by dose-level, and by tumor group) will be tabulated and summarized in this patient population. The grade 3+ adverse events will also be described and summarized in a similar fashion. This will provide an indication of the level of tolerance for this treatment combination in this patient group. | Up to 30 days post-treatment |
| Toxicity profile defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment (Cohorts I and II) | Non-hematologic toxicities will be evaluated via the ordinal Common Terminology Criteria (CTC) standard toxicity grading. Hematologic toxicity measures of thrombocytopenia, neutropenia, and leukopenia will be assessed using continuous variables as the outcome measures (primarily nadir) as well as categorization via CTC standard toxicity grading. Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses. | Up to 30 days post-treatment |
| Overall survival (OS) (Cohort I and II) | OS will be summarized descriptively using the Kaplan-Meier estimate up to 3 years of follow-up in all alive patients. | From registration until death due to any cause, assessed up to 3 years |
| Change in muscle area at the L3 level using a computed tomography (CT) scan (Cohort II) | Changes will be described using summary statistics and graphical techniques. A grayscale pixel histogram of the remaining muscle in the image will be constructed and summed. The number of pixels will then be converted to an area measurement in squared centimeters. All measurements and calculations for each image will be undertaken by two independent study personnel, and the average will be used in the analyses. A Wilcoxon rank sum test may be used as appropriate to compare percent changes of biomarkers between the muscle clinical responders and the non-responders based on CT scan measurements of muscle. | Baseline to day 28 |
| Response rate (Cohort II) | Response rate will be assessed using standard Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria. | At 1 month post-treatment |
| Change in muscle area at the L3 level using a computed tomography scan (Cohort II) | Changes will be described using summary statistics and graphical techniques. A grayscale pixel histogram of the remaining muscle in the image will be constructed and summed. The number of pixels will then be converted to an area measurement in squared centimeters. All measurements and calculations for each image will be undertaken by two independent study personnel, and the average will be used in the analyses. A Wilcoxon rank sum test may be used as appropriate to compare percent changes of biomarkers between the muscle clinical responders and the non-responders based on CT scan measurements of muscle. | Baseline to day 35 |
| Changes in fist-grip strength as measured by hand dynamometer (Cohort II) | Changes will be described using summary statistics and graphical techniques. Patients will use 3 successive tries, and the average value will be used. | Baseline to day 28 |
| Changes in fist-grip strength as measured by hand dynamometer (Cohort II) | Changes will be described using summary statistics and graphical techniques. Patients will use 3 successive tries, and the average value will be used. | Baseline to day 35 |
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.
Ages Eligible for Study:
ALL
Sexes Eligible for Study:
18 Years
Accepts Healthy Volunteers:
This is where you will find people and organizations involved with this study.
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
No publications available
